# Malignant cell receptor-ligand subtypes guide the prediction of prognosis and personalized immunotherapy of liver cancer

## TL;DR

This study identifies liver cancer subtypes using single-cell RNA data to improve prognosis and personalized immunotherapy.

## Contribution

A novel risk model based on 16 malignant cell receptor-ligand genes for liver cancer prognosis and immunotherapy prediction.

## Key findings

- A 16-gene risk model predicts liver cancer prognosis and correlates with tumor characteristics and immunity.
- SRXN1 gene shows differential expression in hepatocellular carcinoma versus normal liver cells.
- Molecular subtypes based on receptor-ligand genes offer insights for personalized immunotherapy.

## Abstract

Objective: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer.

Methods: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines.

Results: A risk model using 16-gene expression levels predicted liver cancer patients’ prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells.

Conclusion: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.